Proton pump inhibitors for upper gastrointestinal bleeding

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Abstract

Acute upper gastrointestinal bleeding (UGIB) remains a public health burden with a persistent high mortality despite advances in modern day management. Proton pump inhibitors (PPI) as medical therapy is an attractive adjuvant to endoscopic treatment in UGIB but the method and dose of PPI therapy remains controversial. This chapter aims to describe the current evidence addressing acute PPI use in the management of UGIB. It will explore the evidence behind the timing, the dosage and the mode of administration of PPI during initial UGIB management, prior to and immediately following endoscopy, as well as in the short-term following discharge.

Introduction

Acute upper gastrointestinal bleeding (UGIB) remains a common cause of hospitalization with an annual incidence of 78/100′000 population and a reported mortality that decreased in the United States over the last 2 decades from 4.7% to 2.1% [1,2]. UGIB can be categorized into variceal and non-variceal UGIB (NVUGIB) causes, as there are important differences in management strategies. Peptic ulcer (PU) disease remains the most common cause of NVUGIB and hospital admission diagnosis in 2012 among all gastro-intestinal related disorders in the United States [3]. Despite advances in modern day management of UGIB, including optimized use of endoscopic therapy, the morbidity and mortality associated with UGIB remains significant, as does its health economic burden [1,2,4,5]. Medical therapy is an attractive adjuvant to endoscopic treatment in UGIB and acid suppression with the use of high-dose proton pump inhibitors (PPI) remains a cornerstone in the medical management of acute UGIB; the optimal route of administration and dosing however remain controversial [6].

This review summarizes the protective pathophysiological mechanisms and the current evidence pertaining to the efficacy and cost-effectiveness of PPI therapy in the management of UGIB. It will discuss the timing, dosage and the route of administration of PPI during the initial management of UGIB prior and immediately following, as well as in the short-term following discharge.

Section snippets

Proton pump inhibitor and the role of acid suppression

In vitro data have explored the important role of acid in impairing hemostasis and causing clot digestion [7], highlighting the important therapeutic role of acid suppressive drugs in the acute setting of UGIB. Maintenance of a high intragastric pH (above 6.0) during the management of UGIB is indeed warranted, as the ability for platelets to form the primary hemostatic platelet plug is deeply impaired by an acid environment, being reduced by 75% at a pH of 6.8 relative to a pH of 7.4. When the

PPI prior endoscopy

  • •

    PPI started prior to endoscopy only decrease the proportion of patients with high-risk stigmata ulcers and the requirement for endoscopic treatment but do not affect rebleeding or mortality

  • •

    If endoscopic evaluation has to be delayed or cannot be performed, PPI therapy should be started and continued to reduce the risk of further bleeding.

  • •

    When PPI are considered, the high dose iv (80 mg) followed by 8 mg/h should be the preferred regimen

  • •

    Additional data are required to better determine the

Practice points

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    Authoritative guidelines support use of high dose PPI for 3 days after successful endoscopic hemostasis for NVUGIB, in particular high risk peptic ulcer bleeding

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    Additional data are required to prove non-inferiority, let alone equivalence of intermittent (oral/iv) dosing in comparison to continuous infusion of PPI

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    PPI after endoscopy in NVUGIB is a dominant strategy in economic terms, i.e.: more efficacious and less costly

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    In variceal UGIB, only a short 10-day course of a once-daily oral PPI

Conclusion

Adherence to evidence-based practice and ensuring robust quality assurance of UGIB management are crucial for optimizing patient outcomes (Fig. 2). Clear guidelines for adequate PPI use in order to standardize best practices are urgenty required. Although high-dose PPI after endoscopy is unanimously incorporated into guidelines for management of NVUGIB, many gaps persist in our knowledge of best practice for PPI use prior endoscopy and to determine the optimal dosing regimen once the iv regimen

Research agenda

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    Cost effectiveness analysis for PPI use prior endoscopy and better identify who can benefit

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    Additional trials to assess whether intermittent regimens are equivalent to continuous iv PPI use

  • •

    To determine the optimal dosing regimen once the iv PPI regimen is completed in patients with acute NVUGIB undergoing successful hemostasis

Conflicts of interest

None.

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